P873: IXAZOMIB VERSUS LENALIDOMIDE OR IXAZOMIB AND LENALIDOMIDE COMBINATION AS MAINTENANCE REGIMEN FOR TRANSPLANT-INELIGIBLE MULTIPLE MYELOMA: UPDATE OF A MULTI-CENTER PROSPECTIVE STUDY IN CHINA
Authors: Zhe Zhuang, Ying Tian, Lei Shi, Hong Yu, Qinhua Liu, Dongmei Zou, Weiwei Tian, Ru Feng, Fei Dong, Yanping MA, Shuangjiao Liu, Hongmei Jing, Hui Liu, Liangming MA, Wanling Sun, Rong Fu, LI Bao, Yin Wu, Wenming Chen, Junling Zhuang
Journal: HemaSphere (2023)

Topic: 14. Myeloma and other monoclonal gammopathies - Clinical Background: Maintenance therapy (MT) deepens response and prolongs progression free survival (PFS) in patients with newly diagnosed multiple myeloma (NDMM) after frontline regimens. Ixazomib, a 2nd generation oral proteasome inhibitor (PI), has been approved for MT because of its convenience and tolerability. Aims: We conducted this prospective multi-center study to compare the efficacy and safety of Ixazomib (I-MT) or Ixazomib plus Lenalidomide (IL-MT) to Lenalidomide (L-MT) as maintenance regimen in transplant-ineligible NDMM patients. Methods: This study was approved by the Institutional Review Board of Peking Union Medical College Hospital and registered (NCT04217967). NDMM patients were enrolled from 10 centers of North China MM Registry, since September 2019. Patients receiving up to 5-9 cycles of front-line regimens and reaching at least partial response (PR) started MT. If PR was not reached after 4 cycles, 2nd-line induction for 2-5 cycles was conducted till PR was reached. Ixazomib 4mg was given on day 1,8,15. Lenalidomide 25mg was given every other day on days 1–21 in a 28-day cycle. Patients in dual drug group were administrated with both Ixazomib and Lenalidomide, dose as listed above. The primary endpoint was progression free survival (PFS) from MT. Results: A total of 181 patients were enrolled, including 70 in I-MT, 63 in L-MT and 48 in IL-MT. The demographic and clinical characteristics, including gender ratio, age, paraprotein isotype, international staging system (ISS), revised-ISS (R-ISS), were comparable among different MT regimen groups (Table 1). The proportions of deletion 17p, t(4,14) and t(14,16), were slightly higher in IL-MT group. The median follow-up duration since maintenance was 23.9, 24.0 and 18.9 months in I-MT, L-MT and IL-MT, respectively. There were 74.3%, 79.4% and 81.3% of the patients reached very good PR (VGPR) or better before MT, while the rates of deep responses improved to 82.9%, 81.0% and 89.6% during follow-up. Progressive disease (PD) was recorded in 37.2% (N=26) of patients on I-MT, 19.0% (N=12) on L-MT and 29.2% (N=14) on IL-MT, respectively. The median PFS was 25.5m, not reached (NR) and 22.8m, while OS was not reached in all groups. After adjusting for age, high-risk cytogenetics, ISS, front-line induction regimens, and depth of response prior to maintenance by Cox model multivariate analysis, our data suggested that L-MT was correlated with significantly longer PFS comparing to I-MT (p=0.023, HR=0.39), while PFS in IL-MT group was similar to those of the other two groups (p=0.29, HR=0.66, Fig 1). As for safety, the prevalence of peripheral neuropathy in whole cohort was 15.7% on I-MT, 15.9% on L-MT and 18.8% on IL-MT. The incidence of gastrointestinal events was 24.3%, 1.6% and 22.9%, respectively. Hematologic toxicities developed in 5.7%, 9.5% and 10.4% of the patients. Infections were recorded in 10%, 3.2% and 2.0%. Three patients withdrew from I-MT group due to adverse events. While in L-MT and IL-MT group, 0 and 2 patients respectively switched MT regimen due to intolerability. Summary/Conclusion: We design this multi-centered prospective study to evaluate if dual drug maintenance will further strengthen response in non-transplant NDMM patients. Our preliminary data suggest that more clinicians in the real practice are inclined to prescribe IL-MT for high-risk patients. Although it is quite tolerable, whether dual-drug maintenance will provide better survival still needs to be defined.Keywords: Maintenance, Myeloma, Therapy